|Title||Serum metabolomic signatures of plant-based diets and incident chronic kidney disease.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Kim H, Yu B, Li X, Wong KE, Boerwinkle E, Seidelmann SB, Levey AS, Rhee EP, Coresh J, Rebholz CM|
|Journal||Am J Clin Nutr|
|Date Published||2022 Jul 06|
|Keywords||Adult, Biomarkers, Diet, Diet, Vegetarian, Humans, Metabolomics, Plants, Renal Insufficiency, Chronic|
BACKGROUND: Greater adherence to plant-based diets is associated with a lower risk of incident chronic kidney disease (CKD). Metabolomics can help identify blood biomarkers of plant-based diets and enhance understanding of underlying mechanisms.
OBJECTIVES: Using untargeted metabolomics, we aimed to identify metabolites associated with 4 plant-based diet indices (PDIs) (overall PDI, provegetarian diet, healthful PDI, and unhealthful PDI) and incident CKD in 2 subgroups within the Atherosclerosis Risk in Communities study.
METHODS: We calculated 4 PDIs based on participants' responses on an FFQ. We used multivariable linear regression to examine the association between 4 PDIs and 374 individual metabolites, adjusting for confounders. We used Cox proportional hazards regression to evaluate associations between PDI-related metabolites and incident CKD. Estimates were meta-analyzed across 2 subgroups (n1 = 1762; n2 = 1960). We calculated C-statistics to assess whether metabolites improved the prediction of those in the highest quintile compared to the lower 4 quintiles of PDIs, and whether PDI- and CKD-related metabolites predicted incident CKD beyond the CKD prediction model.
RESULTS: We identified 82 significant PDI-metabolite associations (overall PDI = 27; provegetarian = 17; healthful PDI = 20; unhealthful PDI = 18); 11 metabolites overlapped across the overall PDI, provegetarian diet, and healthful PDI. The addition of metabolites improved prediction of those in the highest quintile as opposed to the lower 4 quintiles of PDIs compared with participant characteristics alone (range of differences in C-statistics = 0.026-0.104; P value ≤ 0.001 for all tests). Six PDI-related metabolites (glycerate, 1,5-anhydroglucitol, γ-glutamylalanine, γ-glutamylglutamate, γ-glutamylleucine, γ-glutamylvaline), involved in glycolysis, gluconeogenesis, pyruvate metabolism, and γ-glutamyl peptide metabolism, were significantly associated with incident CKD and improved prediction of incident CKD beyond the CKD prediction model (difference in C-statistics for 6 metabolites = 0.005; P value = 0.006).
CONCLUSIONS: In a community-based study of US adults, we identified metabolites that were related to plant-based diets and predicted incident CKD. These metabolites highlight pathways through which plant-based diets are associated with incident CKD.
|Alternate Journal||Am J Clin Nutr|
|PubMed Central ID||PMC9257476|
|Grant List||RC2 HL102419 / HL / NHLBI NIH HHS / United States |
5RC2HL102419 / / American Recovery and Reinvestment Act /
K01 DK107782 / DK / NIDDK NIH HHS / United States
/ / NIH /
R56 HL153178 / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HH / HHS / United States
R03 DK128386 / DK / NIDDK NIH HHS / United States
3U01HG004402-02S1 / HG / NHGRI NIH HHS / United States
R01 HL153178 / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
/ / Cohorts for Heart and Aging Research in Genomic Epidemiology /